A stochastic single-molecule event triggers phenotype switching of a bacterial cell.
By monitoring fluorescently labeled lactose permease with single-molecule sensitivity, we investigated the molecular mechanism of how an Escherichia coli cell with the lac operon switches from one phenotype to another. At intermediate inducer concentrations, a population of genetically identical cells exhibits two phenotypes: induced cells with highly fluorescent membranes and uninduced cells with a small number of membrane-bound permeases. We found that this basal-level expression results from partial dissociation of the tetrameric lactose repressor from one of its operators on looped DNA. In contrast, infrequent events of complete dissociation of the repressor from DNA result in large bursts of permease expression that trigger induction of the lac operon. Hence, a stochastic single-molecule event determines a cell's phenotype.
Choi
Paul J
PJ
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Cai
Long
L
Frieda
Kirsten
K
Xie
X Sunney
XS
D001426:Bacterial Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism*; D025461:Feedback, Physiological; D015964:Gene Expression Regulation, Bacterial; D007763:Lac Operon; D056968:Lac Repressors; D007785:Lactose / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D009875:Operator Regions, Genetic; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D013269:Stochastic Processes; D027981:Symporters / Q000235:genetics* / Q000378:metabolism*
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D056968:Lac Repressors; C539064:LacI protein, E coli; C050221:LacY protein, E coli; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D027981:Symporters; D007785:Lactose